ArticleFrontiers in pharmacology2026
PACSIN2 regulates mercaptopurine cytotoxicity and cellular biomechanics through Rac1 modulation in intestinal epithelial cells.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Mercaptopurine (MP) is used to treat pediatric acute lymphoblastic leukemia and inflammatory bowel disease (IBD). The Protein Kinase C and Casein Kinase Substrate in Neurons 2 (PACSIN2) rs2413739 polymorphism is an expression-quantitative trait locus associated with reduced PACSIN2 expression in gastrointestinal tissues and thiopurine-related gastrointestinal toxicity. PACSIN2 interacts with Rac1, a key thiopurine target protein involved in cytoskeletal regulation. Methods: LS180 intestinal cells with stable PACSIN2 knockdown (KD) or transient overexpression were used to assess the role of PACSIN2 in regulating Rac1 under basal conditions and after MP exposure. Rac1 levels and activity were measured by Western blot and G-LISA assay, respectively. Cytotoxicity was evaluated by MTT assay following exposure to MP and the Rac1 inhibitor NSC23766. Cell stiffness was assessed by atomic force microscopy, and cytoskeletal organization was examined by immunofluorescence. Results: PACSIN2 KD cells exhibited elevated Rac1 expression and activity, and increased sensitivity to MP, which was further augmented by the Rac1 inhibitor NSC23766. Conversely, PACSIN2 overexpression reduced Rac1 levels and conferred MP resistance. PACSIN2 depletion decreased cell stiffness affecting the cytoskeletal architecture, particularly impairing tubulin levels and actin distribution. MP exposure reduced cell stiffness and decreased both Rac1 expression and activity across all tested cell lines, with more pronounced effects in LS180 KD cells. Altered cytoskeletal organization, especially actin redistribution, correlated with changes in cellular biomechanical properties and drug sensitivity. Conclusion: These findings suggest that PACSIN2 modulates MP response by regulating Rac1 levels and cytoskeletal integrity, providing a molecular basis for the clinical association between PACSIN2 and thiopurine-related gastrointestinal toxicity. These insights may contribute to the development of personalized approaches to optimize thiopurine therapy in pediatric patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.